Changes that may occur in the expression of protein and mRNA for transforming growth factor-beta (TGF-beta) isoforms in response to various disease states and tissue treatments are being investigated using immunohistochemistry and Northern blot techniques. For example, there is an increase in expression of TGF-beta1 protein in prostatic carcinoma, as compared to benign prostatic hyperplasia, in both humans and in a mouse model of the disease. There is also increased expression of extracellular TGF-beta1 protein in human breast cancer following tamoxifen treatment, and in human prostate cancer following androgen ablation or treatment with LH-RH agonists. There is increased expression of TGF-beta2 in astrocytes in brains from patients with familial and sporadic Alzheimer's disease when compared to controls. There is also expression of TGF-beta2 in amyloid plaques and neurons exhibiting neurofibrillary tangles. Analysis of immunoreactive TGF-beta3 in neurons in patients and controls is in progress. Some of the protective effects of TGF-beta in tissues may be mediated by decreased levels of oxygen-free radicals. In endothelial cells and cardiomyocytes, it appears that TGF- beta can decrease mRNA expression of xanthine oxidase which is involved in generation of oxygen-free radicals. There appears to be little effect of TGF-beta on enzymes involved in clearance of oxygen-free radicals. Primary neuronal cultures are being developed to determine if TGF-beta can protect these cells from reported damaging effects of beta-amyloid protein. This may be one of the functions of increased immunoreactive TGF-beta seen in brains of Alzheimer's disease patients.